Proliferative enteropathy, also known as ileitis, is a common enteric disease of post-weaned pigs worldwide, caused by the obligate intracellular bacterium Lawsonia intracellularis. The characteristic lesion is a proliferation of immature enterocytes in the ileal intestinal crypts; these cells usually contain the causative bacteria within their apical cytoplasm. At autopsy, histologic lesions can be confirmed as Lawsonia-positive by visualization of 1.5-2.5 μm long, vibrioid shaped bacteria especially in enterocytes, but also often within macrophages located in the lamina propria between crypts, and in mesenteric lymph nodes. Clearance of the bacteria from the enterocytes leads to resolution of the associated proliferative lesions, indicating a direct local effect of the bacteria on the crypts (McOrist et al., Developed and resolving lesions in porcine proliferative enteropathy: possible pathogenetic mechanisms, Journal of Comparative Pathology, 115, 1996, pp 35-45). The presence of Lawsonia intracellularis in these lesions has been demonstrated using PCR, both in animals manifesting disease (i.e. show diarrhea or abnormal red-black tarry faeces, potentially resulting in death) as in animals manifesting only subclinical infection (not showing diarrhoea or abnormal faeces). Clinical cases are usually present in the grower-finisher period; in some older finisher pigs an acute hemorrhagic form has been recorded.
The relationship between Lawsonia intracellularis seropositive pigs and the proportion of pigs presenting clinical or subclinical infection has been studied before (Van der Heijden, Prevalence of exposure and infection of Lawsonia intracellularis among slaughter-age pigs., Res Vet Sci, December 2004, 77(3), pp 197-202). It appears that some pigs could be carriers, i.e. are infected but present no clinical signs of ileitis. In particular in Europe, animals which are considered to be free of disease, appear to have subclinical infections, as evidenced by remains of the bacteria at slaughter in the intestines. An explanation for the positive results regarding the presence of Lawsonia intracellularis bacteria in clinical disease free herds is that those herds have Lawsonia intracellularis moving through their finisher groups. Only in certain situations, the Lawsonia infection results in clinical problems, including acute haemorrhagic enteropathy cases.
In clinical disease free herds vaccination against Lawsonia infection is uncommon. However, since it is known that subclinical infection may lead to a negative impact on average daily weight gain (ADWG) of a pig, some grower-finisher farms use the sole commercial Ileitis vaccine in the market, i.e. ENTERISOL® Ileitis (a Lawsonia Intracellularis vaccine comprising an avirulent live culture, available from Boehringer Ingelheim), to combat local infection in the intestines. This vaccine contains live attenuated Lawsonia intracellularis bacteria and is administered orally. Indeed, at present it is believed that a local infection of the gut can only be fought by inducing local immunity. This is different for animals which present clinical disease. It has been shown (WO 2009/144088, assigned to Intervet International BV) that those animals can be successfully protected by systemic vaccination with a non-live vaccine. Without being bound to theory, it is believed that the reason for this is that those animals have severe gastro-intestinal lesions that expose the infection to the system, which would explain why a systemic immune response would help to combat the infection. However, when there is only a subclinical infection, corresponding to a minor local infection of the gut, a local immune response including IgA and cellular immunity is believed to be needed to combat the infection. For this one needs a vaccine comprising live bacteria, administered locally. This is confirmed in the paper of Mike Roof called The Research and Development of Enterisol® Ileitis, presented at the European Enterisol® Ileitis Symposium, Oct. 13-15, 2005, Barcelona, Spain. On page 2 it is indicated in Table 1.1 that although a killed vaccine administered systemically might induce “Humoral/systemic immunity”, it fails to induce both “Mucosal immunity” and “Cell mediated immunity”. The latter two being commonly known as needed to combat a local infection of the gut with intracellular pathogens (Ivan Roitt, Essential Immunology, seventh edition, 1991, pages 206 “The secretory immune system protects the external mucosal surfaces”, 209 “Defence is by cell-mediated immunity” and 210 “Activated macrophages kill intracellular parasites”). In the Mike Roof paper of 2005 it is stated that “Early investigations looking at killed bacterin prototype confirmed . . .that killed vaccines provided no protective response against . . .the colonization of the gut.” (page 2, left hand column, second full paragraph).
The live vaccine ENTERISOL® Ileitis is indeed licensed with a claim to reduce loss of weight gain associated with infection, and is used for that purpose. Disadvantages of this vaccine are that it needs to be administered orally, which is not a routine way of vaccinating pigs, and that one has to interrupt use of antimicrobials in the animals for six days (since otherwise the bacteria in the vaccine might be killed). Another disadvantage is that the vaccine is not licensed for the reduction of shedding of the bacteria. Apparently, data used for the marketing authorization did not show a reduction in shedding of the bacteria. A recent publication (Riber et al. in Vaccine 33, 2015, 156-162) confirmed that ENTERISOL® Ileitis provides no protection at all against shedding of Lawsonia bacteria after infection. This might indicate that an infection with Lawsonia intracellularis in a herd of animals might remain even though all animals are vaccinated and weight gain problems and clinical manifestations are significantly reduced.